ABSTRACT Surgery is a common process ? with some 43 million individuals undergoing surgery in the United States every year. Depending on their premorbid and intraoperative processes, Individuals are vulnerable to acute postoperative pain and more importantly in some 30% to chronic neuropathic pain that contributes to significant morbidity. While general anesthesia provides a state of unconsciousness, there are no objective measures of evoked or ongoing pain (i.e., analgesia) while under anesthesia. The lack of analgesic control while under anesthesia may induce a response in the brain called central sensitization that is the harbinger of two main deleterious outcomes: (1) increased pain and use of opioids in the postoperative period, and (2) the initiation of a chronic neuropathic pain process (that may also be driven by the nerve damage from the surgical incisions ? peripheral sensitization). In this proposal we will introduce a novel mechanistic approach to the assessment of nociceptive drive (both evoked pain and ongoing pain) in the perioperative period (i.e., during surgery and in the postoperative period). We will use functional Near-Infrared Spectroscopy (fNIRS) to define evoked pain and ongoing pain (i.e., an objective, quantitative assessment of analgesia in a surgical environment). The combination will allow us to measure the Nociceptive Load during surgery. We hypothesize that there is a correlation of the pain load and the postoperative course as measured by postoperative pain levels, postoperative analgesic use. In order to do this we have 2 Specific Aims: (1) fNIRS Measures of Opioid Blockade of Nociceptive Signals on Pain Load under Anesthesia; and (2) Define fNIRS Differences in Pain Load (Evoked and Ongoing Pain) in the Perioperative (surgery and post surgery) in patients undergoing knee arthroscopy who have inhalational anesthesia alone vs. inhalational anesthesia + regional blockade. We have the necessary team that has worked together for many years (NIRS physicists, neurobiologists, pain specialists, anesthesiologists and psychologist), equipment, publications, preliminary data and hospital support to successfully carry out the proposed work. The successful completion of this research will provide a basis for future studies that may provide: (1) Objective Measurement of Analgesic Depth and Pain Load during surgery utilizing fNIRS; (2) Relative significance of continuous and repeated noxious events on pain load and clinical outcomes (2) Objective Measurement of different anesthetics on Pain Load.